HIV, the causative agent of AIDS, selectively infects CD4+ T cells and macrophages, incapacitates the immune system, and results in opportunistic infections, neoplasms and death. Because T cell mediated immunity (CMI) plays a major role in resistance to infections and recovery from disease by a variety of envelope viruses, it is likely that an effective vaccine against HIV should induce strong HIV specific T CMI responses and perhaps antibodies which, in the presence of complement (C) or by ADCC, can lyse HIV infected cells. The goals of these studies are thus to; 1 and 2) evaluate humans and non-human primates immunized with candidate HIV vaccines for HIV specific T helper (Th) cytotoxic T cells (CTL) and cytotoxic antibodies; 3) evaluate macaques immunized with candidate vaccines against Simian Immunodeficiency Virus (SIV), which causes AIDS in macaques) for SIV-specific , The CTL and cytotoxic antibodies; 4) compare HIV infected chimpanzees (which do not develop AIDS) with humans for the presence of HIV responses; 5) determine whether HIV infected humans or SIV infected macaques have circulating CTL which can lyse normal CD4+ cells (perhaps contributing to the loss of CD4+ cells during infection) and attempt to define the target antigens for these CTL; 6) determine whether in victor stimulation of human, chimp or macaque T cells with pooled allogeneic normal cells can result in CTL lytic for autologous HIV or SIV infected cells; 7) produce and evaluate HIV- 1 isolates, cross-linked to MAb to CD3 or CD16 on lymphocytes, for their ability to focus human or chimp PBL to lyse HIV-1 infected cells and to produce MAb heteroconjugates reactive with HIV-1 and SIV and determine if they enable human an macaque PBL to lyse HIV- 2 and SIV infected cells. The first four aims of this proposal related to the development of vaccines against immunodeficiency viruses and elucidation of antigens which elicit Th and CTL responses. The fourth and fifth aims concern possible differences of HIV CMI immune responses and autoimmunity between chimps and humans infected with HIV and may relate to the fact that HIV causes disease in humans but not in chimps. The fifth, sixth and seventh aims may provide results leading to immunotherapeutic approaches for HIV infections.